Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration

The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC...

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Veröffentlicht in:Cell stem cell Jg. 14; H. 2; S. 149
Hauptverfasser: Metcalfe, Ciara, Kljavin, Noelyn M, Ybarra, Ryan, de Sauvage, Frederic J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 06.02.2014
Schlagworte:
Adenomatous Polyposis Coli Protein - metabolism
Animals
Colitis - chemically induced
Colitis - pathology
Dextran Sulfate
Diphtheria Toxin - pharmacology
Dose-Response Relationship, Radiation
Hyperplasia
Intestines - drug effects
Intestines - physiology
Intestines - radiation effects
Mice
Models, Animal
Paneth Cells - cytology
Paneth Cells - drug effects
Paneth Cells - radiation effects
Radiation, Ionizing
Receptors, G-Protein-Coupled - metabolism
Regeneration - drug effects
Regeneration - radiation effects
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - radiation effects
ISSN:1875-9777, 1875-9777
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Zusammenfassung:The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5(-) reserve stem cells are radiosensitive and that Lgr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2013.11.008